Also known as: 1401708-83-5, L-Isoleucinamide, N-(1-oxohexyl)-L-tyrosyl-N-(6-amino-6-oxohexyl)-, 9WYX65A5C2, PNB-0408, DTXSID701032895, ATH-1001, 6-(2-(2-Hexanamido-3-(4-hydroxyphenyl)propanamido)-3-methylpentanamido)hexanamide, N-(1-OXOHEXYL)-L-TYROSYL-N-(6-AMINO-6-OXOHEXYL)-L-ISOLEUCINAMIDE
Dihexa (1401708-83-5, L-Isoleucinamide, N-(1-oxohexyl)-L-tyrosyl-N-(6-amino-6-oxohexyl)-, 9WYX65A5C2) is classified under other / experimental, sold for research use only and not approved for human consumption.
Aggregated from the cited literature below. We summarize sources — we don't author claims.
Dihexa (also described as an N-hexanoic-tyrosine-isoleucine-(6) aminohexanoic amide; aliases include PNB-0408 and ATH-1001 in the provided prompt) is discussed in research as a blood-brain barrier–permeable analog of angiotensin IV (AngIV). Several provided sources associate its procognitive/antidementia activity with signaling involving hepatocyte growth factor (HGF) and the c-Met receptor, including effects on hippocampal synaptogenesis/spinogenesis and memory-related behavioral outcomes in animal models. Other provided sources also discuss Dihexa within small-molecule differentiation strategies for hepatic cells in vitro and within broader review contexts (orthopedics; cognitive effects of AngIV-related peptides; and HGF/c-Met as a therapeutic target in Alzheimer’s disease).
Mechanism (as reported)
Research described in the sources indicates that dihexa binds with high affinity to hepatocyte growth factor (HGF), induces c-Met phosphorylation, and promotes HGF-dependent cell scattering; these effects were reported to be inhibited by an HGF antagonist and by c-Met knockdown. The same study reported that dihexa and its parent AngIV-related compound induced hippocampal spinogenesis and synaptogenesis similar to HGF itself, and that blocking HGF reduced dihexa’s procognitive effect in a Morris water maze learning task. Additional review sources describe the HGF/c-Met receptor system as a target associated with synaptogenesis and neurogenesis, and relate dihexa to this pathway.
Key findings (each cites a source)
A study reported that dihexa is an orally active, blood-brain barrier–permeable analog of an AngIV-related molecule and investigated its procognitive mechanism. [PMID 25187433]
A study reported that dihexa binds with high affinity to hepatocyte growth factor (HGF) and that dihexa (and its parent compound Norleucine 1-AngIV) induced c-Met phosphorylation and augmented HGF-dependent cell scattering. [PMID 25187433]
A study reported that dihexa and Norleucine 1-AngIV induced hippocampal spinogenesis and synaptogenesis similar to HGF, and that these actions were inhibited by an HGF antagonist and by c-Met knockdown. [PMID 25187433]
A study reported that blocking HGF (using an HGF antagonist delivered intracerebroventricularly) blocked the procognitive/antidementia capacity of orally delivered dihexa in the Morris water maze spatial learning task. [PMID 25187433]
A review summarized information linking the HGF/c-Met receptor system to Alzheimer’s disease treatment approaches, and stated that stimulation by an angiotensin-based analogue Dihexa induced dendritic arborization and synaptogenesis and was associated with memory facilitation in animal models. [PMID 25649658]
A systematic review reported that in experimental (non-human) studies, AngIV and AngIV analogs (including dihexa) were associated with improved performance on spatial working memory and passive avoidance tasks in cognitive deficit models. [PMID 29733881]
A study described chemical modification of an AngIV analog to produce a metabolically stabilized, orally active, blood-barrier permeant analog (dihexa) and reported antidementia activity in scopolamine and aged rat models as well as marked synaptogenic activity. [PMID 23055539]
A review reported development of small-molecule AngIV analogs aimed at Alzheimer’s and Parkinson’s diseases and described dihexa as showing promise by augmenting synaptic connectivity via formation of new functional synapses. [PMID 25455861]
A small-molecule strategy study reported that combining Vitamin C, Dihexa, and Forskolin (VDF) could substitute growth factors to induce hepatic specification from human pluripotent stem cells, leading to hepatoblast formation and functional hepatocyte-like cells in vitro and functional behavior described in vivo. [PMID 35410439]
A review on orthopaedic therapeutic peptides mentioned neuroactive peptides such as dihexa and described them as targeting brain-derived neurotrophic factor and HGF/c-Met pathways relevant to neuroplasticity (as presented in that review). [PMID 41490200]
A study on radiolabeled dimeric alpha-MSH analogs included dimeric peptide constructs containing a “diHexa” motif and reported that although the dimers showed increased receptor affinity and excellent internalization in vitro, tumor-to-kidney ratios in vivo were less favorable compared with a monomeric standard, with marked kidney uptake described as an unfavorable factor. [PMID 18097939]
Independent test grades
No independent third-party test data is available for Dihexa yet. Our test grades are aggregated from Finnrick, which independently tests a subset of research peptides — many approved drugs and newer or niche compounds aren't covered.
Research literature (9)
Consolidated from PubMed — each links to the original record.
Bapst JP, Froidevaux S, Calame M, Tanner H, Eberle AN · Journal of receptor and signal transduction research · 2007 · PMID 18097939
FAQ
What is Dihexa?
Dihexa (1401708-83-5, L-Isoleucinamide, N-(1-oxohexyl)-L-tyrosyl-N-(6-amino-6-oxohexyl)-, 9WYX65A5C2) is classified under other / experimental, sold for research use only and not approved for human consumption. Research goals associated with it include cognitive & mood.
Is Dihexa FDA-approved?
No. Dihexa is sold for research use only and is not approved for human consumption.
What does the research on Dihexa say?
peptideone aggregates 9 references from PubMed for Dihexa. The summary on this page digests them with citations; we summarize sources and make no efficacy claims.